Efficacy and Safety of Sarilumab in Hospitalized Patients With Coronavirus Disease 2019: A Randomized Clinical Trial
Sumathi Sivapalasingam, David J. Lederer, Rafia Bhore, Negin Hajizadeh, Gerard J. Criner, Romana Hosain, Adnan Mahmood, Angeliki Giannelou, Selin Somersan-Karakaya, Meagan P. O’Brien, Anita Boyapati, Janie Parrino, Bret J. Musser, Emily Labriola–Tompkins, Divya Ramesh, Lisa A. Purcell, Daya Gulabani, Wendy Kampman, Alpana Waldron, Michelle N. Gong, Suraj Saggar, Steven J. Sperber, Vidya Menon, David Stein, Magdalena E. Sobieszczyk, William Park, Judith A. Aberg, Samuel M. Brown, Jack A. Kosmicki, Julie Horowitz, Manuel A. R. Ferreira, Aris Baras, Bari Kowal, A. Thomas DiCioccio, Bolanle Akinlade, Michael C. Nivens, Ned Braunstein, Gary Herman, George D. Yancopoulos, David M. Weinreich
Abstract
BACKGROUND: Open-label platform trials and a prospective meta-analysis suggest efficacy of anti-interleukin (IL)-6R therapies in hospitalized patients with coronavirus disease 2019 (COVID-19) receiving corticosteroids. This study evaluated the efficacy and safety of sarilumab, an anti-IL-6R monoclonal antibody, in the treatment of hospitalized patients with COVID-19. METHODS: In this adaptive, phase 2/3, randomized, double-blind, placebo-controlled trial, adults hospitalized with COVID-19 received intravenous sarilumab 400 mg or placebo. The phase 3 primary analysis population included patients with critical COVID-19 receiving mechanical ventilation (MV). The primary outcome was proportion of patients with ≥1-point improvement in clinical status from baseline to day 22. RESULTS: There were 457 and 1365 patients randomized and treated in phases 2 and 3, respectively. In phase 3, patients with critical COVID-19 receiving MV (n = 298; 28.2% on corticosteroids), the proportion with ≥1-point improvement in clinical status (alive, not receiving MV) at day 22 was 43.2% for sarilumab and 35.5% for placebo (risk difference, +7.5%; 95% confidence interval [CI], -7.4 to 21.3; P =.3261), a relative risk improvement of 21.7%. In post hoc analyses pooling phase 2 and 3 critical patients receiving MV, the hazard ratio for death for sarilumab vs placebo was 0.76 (95% CI, .51 to 1.13) overall and 0.49 (95% CI, .25 to .94) in patients receiving corticosteroids at baseline. CONCLUSIONS: This study did not establish the efficacy of sarilumab in hospitalized patients with severe/critical COVID-19. Post hoc analyses were consistent with other studies that found a benefit of sarilumab in patients receiving corticosteroids. CLINICAL TRIALS REGISTRATION: NCT04315298.